Field of the Invention
The invention relates to a method of capturing Circulating Tumor Cells from a sample, and a microfluidic device for performing the method.
Brief Description of Related Technology
Cancer remains one of the world's most devastating diseases, with more than 10 million new cases every year. Although recent advances in diagnostic and therapeutic methods to treat primary tumors have resulted in a decrease in mortality of cancer for the past two years, metastasis of cancer still poses a great challenge as patients often relapse. Disseminated and Circulating tumor cells (DTCs and CTCs, respectively) are known to induce secondary tumor formation at distant sites from primary tumors, known as metastasis. Two major theories describing cancer metastasis, the seed and soil hypothesis and the mechanical trapping theory, are available and the extravasation process for each are similar, consisting of three sequential steps. The metastasis mechanism is known to be initiated by cell rolling the naturally occurring process utilized to recruit leukocytes to sites of inflammation. In the second step, the cells firmly attach to the endothelial cells. In the third step, the cells transmigrate through the endothelium (diapedesis), resulting in secondary tumor formation.
Research efforts on diagnosis and prognosis of metastatic cancer have concentrated on the detection of DTCs in bone marrow (BM) and CTCs in blood. Detection of DTCs requires aspiration of BM—a process that is invasive, time-consuming, and often painful for the patients, precluding repeated samplings that are necessary for prognosis studies along with therapeutic treatments. Consequently, effective detection of CTCs in peripheral blood of cancer patients holds a promise as an alternative due to its minimal invasiveness and easy samplings (i.e. blood drawing). However, the clinical usage of CTCs has not yet been implemented for routine clinical practice. In fact, the clinical significance of CTCs in patient blood is less clear than that for DTCs in BM. Unlike DTCs in BM that are relatively easy to enrich using Ficoll-based assays or the OncoQuick approach, and other immunomagnetic enrichment procedures, CTCs are extremely rare (estimated to be in the range of one tumor cell in the background of 106-109 normal blood cells), presenting a tremendous challenge for efficient, clinically significant detection of CTCs.
Thus, there exists in the art a need for devices and methods to efficiently isolate circulating tumor cells with enhanced sensitivity and specificity to aid in diagnosis and prognosis of cancer.